Mitochondrial-Targeted Phytochemicals in Reproductive Aging: Mechanisms and Translational Potential

Reproductive aging is increasingly recognized as a major contributor to infertility in both women and men. Although traditionally linked to endocrine decline, emerging evidence suggests that mitochondrial dysfunction is a central mechanism underlying impaired gamete quality and reduced reproductive capacity. This review aimed to evaluate the role of mitochondrial deterioration in reproductive aging and to examine the therapeutic potential of mitochondrial-targeted phytochemicals.

A narrative review of experimental, translational, and clinical studies was conducted focusing on mitochondrial dynamics, oxidative stress, bioenergetic impairment, and phytochemical-based interventions in reproductive aging. Relevant evidence involving oocytes, spermatozoa, and the reproductive microenvironment was critically synthesized.

Aging-associated mitochondrial dysfunction was consistently associated with impaired ATP production, excessive reactive oxygen species generation, mitochondrial DNA damage, and disrupted cellular homeostasis, leading to reduced oocyte competence, sperm motility, and embryonic development. Several phytochemicals, including resveratrol, quercetin, epigallocatechin gallate, astaxanthin, lycopene, berberine, and coenzyme Q10, demonstrated protective effects through modulation of SIRT1-PGC-1α, AMPK, Nrf2, and PINK1-Parkin signaling pathways.

Targeting mitochondrial bioenergetics with phytochemicals may provide a promising strategy for preserving fertility and extending reproductive lifespan, although further large-scale clinical validation is required.